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51.
A New Class of 1‐Aryl‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline Derivatives as Reversers of P‐Glycoprotein‐Mediated Multidrug Resistance in Tumor Cells 下载免费PDF全文
Alisa A. Nevskaya Maria D. Matveeva Prof. Tatiana N. Borisova Dr. Mauro Niso Prof. Nicola A. Colabufo Dr. Angelina Boccarelli Dr. Rosa Purgatorio Dr. Modesto de Candia Prof. Saverio Cellamare Prof. Leonid G. Voskressensky Prof. Cosimo D. Altomare 《ChemMedChem》2018,13(15):1588-1596
A number of aza‐heterocyclic compounds, which share the 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ) scaffold with members of the lamellarin alkaloid family, were synthesized and evaluated for their ability to reverse in vitro multidrug resistance in cancer cells through inhibition of P‐glycoprotein (P‐gp) and/or multidrug‐resistance‐associated protein 1. Most of the investigated DHPIQ compounds proved to be selective P‐gp modulators, and the most potent modulator, 8,9‐diethoxy‐1‐(3,4‐diethoxyphenyl)‐3‐(furan‐2‐yl)‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline‐2‐carbaldehyde, attained sub‐micromolar inhibitory potency (IC50: 0.19 μm ). Schiff bases prepared by the condensation of some 1‐aryl‐DHPIQ aldehydes with p‐aminophenol also proved to be of some interest, and one of them, 4‐((1‐(4‐fluorophenyl)‐5,6‐dihydro‐8,9‐dimethoxypyrrolo[2,1‐a]isoquinolin‐2‐yl)methyleneamino)phenol, had an IC50 value of 1.01 μm . In drug combination assays in multidrug‐resistant cells, some DHPIQ compounds, at nontoxic concentrations, significantly increased the cytotoxicity of doxorubicin in a concentration‐dependent manner. Studies of structure–activity relationships and investigation of the chemical stability of Schiff bases provided physicochemical information useful for molecular optimization of lamellarin‐like cytotoxic drugs active toward chemoresistant tumors as well as nontoxic reversers of P‐gp‐mediated multidrug resistance in tumor cells. 相似文献
52.
We demonstrate the possibility to selectively reduce insulating fluorinated graphene to conducting and semiconducting graphene by electron beam irradiation. Electron-irradiated fluorinated graphene microstructures show 7 orders of magnitude decrease in resistivity (from 1 TΩ to 100 kΩ), whereas nanostructures show a transport gap in the source-drain bias voltage. In this transport gap, electrons are localized, and charge transport is dominated by variable range hopping. Our findings demonstrate a step forward to all-graphene transparent and flexible electronics. 相似文献
53.
Roberto Olmi Viacheslav V Meriakri Amleto Ignesti Saverio Priori Cristiano Riminesi 《The Journal of microwave power and electromagnetic energy》2007,41(3):37-49
The dielectric properties of water solutions of ethanol and sugar are investigated in the microwave region with the objective of setting up a method for the quality control of the fermentation process of alcoholic beverages. Alcoholic fermentation is the process by which carbohydrates, in particular sugar, are converted by the yeast into alcohol. During that process several other by-product compounds are produced, including a significant amount of carbon dioxide. The fermentation stage is of fundamental importance in the production of alcoholic beverages because some of the by-products' components have a considerable effect on the flavour, aroma, and other characteristic properties of the beverages. The on-line monitoring of the fermentation process can thus be very useful for controlling the timing and the development of the process in order to correct it earlier if deviations from "normality" occur. Dielectric spectroscopy is shown to be suitable for such a task, being able to discriminate between the initial water-sugar mixture and the final water-alcohol solution and making it possible to detect the production of carbon dioxide during fermentation. A case-study consisting of the monitoring of the primary fermentqtion of beer by dielectric spectroscopy is presented and discussed. 相似文献
54.
Samples of polycaprolactam, obtained by anionic polymerization of caprolactam in bulk under adiabatic conditions and in presence of different amounts of lithium chloride, have been fractionated using a method based on summative fractionation of the polyamide in the amorphous state. By increasing the amount of lithium chloride in the system, the limiting viscosity number of the as-polymerized material decreases; at the same time the integral distribution curves reveal a bimodal molecular weight distribution as a consequence of the complex pattern of main and side reactions. The high molecular weight peak is very narrow, both with and without lithium chloride in the polymerizing system. Lithium chloride considerably reduces the polydispersity of the low molecular weight portion, which is very broad for the non-salt treated polycaprolactam. The relative importance of the two peaks, which is almost even for polycaprolactam synthesized without salt, is shifted in favour of the lower molecular weight peak by increasing the salt content. This effect is also accompanied by a higher production of water-soluble oligomers. 相似文献
55.
Ruiu G Pinach S Veglia F Gambino R Marena S Uberti B Alemanno N Burt D Pagano G Cassader M 《Lipids》2009,44(2):153-160
Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due
to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption
on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression
in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind
randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols
(equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The
effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly
increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched
yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity
and the reduction in CD36 expression may reflect an important antiatherogenic effect. 相似文献
56.
Jessica Maiuolo Irene Bava Cristina Carresi Micaela Gliozzi Vincenzo Musolino Miriam Scicchitano Roberta Macri Francesca Oppedisano Federica Scarano Maria Caterina Zito Francesca Bosco Stefano Ruga Saverio Nucera Sara Ilari Ernesto Palma Carolina Muscoli Vincenzo Mollace 《International journal of molecular sciences》2021,22(15)
In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 μg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 μg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena. 相似文献
57.
Saverio Candido Barbara Maria Rita Tomasello Alessandro Lavoro Luca Falzone Giuseppe Gattuso Massimo Libra 《International journal of molecular sciences》2021,22(18)
IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients. 相似文献
58.
Alessandro Cardillo Gaetano Cascini Francesco Saverio Frillici Federico Rotini 《Engineering with Computers》2013,29(3):287-306
In a recent project the authors have developed an approach to assist the identification of the optimal topology of a technical system, capable of overcoming geometrical contradictions that arise from conflicting design requirements. The method is based on the hybridization of partial solutions obtained from mono-objective topology optimization tasks. In order to investigate efficiency, effectiveness and potentialities of the developed hybridization algorithm, a comparison among the proposed approach and traditional topology optimization techniques such as Genetic Algorithms (GAs) and gradient-based methods is presented here. The benchmark has been performed by applying the hybridization algorithm to several case studies of multi-objective optimization problems available in literature. The obtained results demonstrate that the proposed approach is definitely less expensive in terms of computational requirements, than the conventional application of GAs to topology optimization tasks, still keeping the same effectiveness in terms of searching the global optimum solution. Moreover, the comparison among the hybridized solutions and the solutions obtained through GAs and gradient-based optimization methods, shows that the proposed algorithm often leads to very different topologies having better performances. 相似文献
59.
Saverio Latorrata Paola Gallo StampinoCinzia Cristiani Giovanni Dotelli 《International Journal of Hydrogen Energy》2014
Microporous layers (MPLs) obtained from inks containing three fluorinated polymers (perfluoroalcoxy, fluorinated ethylene propylene and a fluorinated polyurethane based on perfluoropolyether blocks) replacing conventional PTFE were prepared. Inks composition and rheological behaviour were fixed in order to apply the blade coating technique for MPL deposition. Superhydrophobic layers were obtained since contact angles higher than 150° were measured. The samples, tested in a single fuel cell at lab scale, at 60 °C and different relative humidity (RH 80/100 and 80/60, hydrogen/air) evidenced that new polymers are able to improve electrical performances reaching maximum power density values higher than those showed by conventional MPLs based fuel cells. Electrochemical impedance spectroscopy (EIS) was also carried out on the running cell using a Frequency Response Analyzer to assess the different dissipation phenomena and related losses. 相似文献
60.
Marco Andreini Mauro Caciolai Saverio La Mendola Lamberto Mazziotti Mauro Sassu 《火与材料》2015,39(1):41-57
An experimental campaign is presented to determine the effects of high temperatures on the mechanical properties of several materials for masonry walls (blocks and mortars), testing a series of cylindrical specimens (diameter of 100 mm and height of 200 mm). After compression tests at 20 °C, an experimental procedure was designed for high‐temperature testing. The cylindrical samples were heated in a muffle furnace, then were inserted into a specific apparatus (called ‘thermos’) for maintaining the prescribed temperature, and finally were subjected to a mechanical compression test. The results obtained by applying this procedure show a common variation of the strength, reduction of modulus of elasticity, and corresponding increments of the ultimate strain with temperature enhancement. Specific diagrams and discussion on the results are performed for each material. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献